Streptococcus pyogenes

Taxonomic Classification

Kingdom: Bacteria Phylum: Firmicutes Class: Bacilli Order: Lactobacillales Family: Streptococcaceae Genus: Streptococcus Species: Pyogenes

Background

Streptococcus pyogenes is a species of Streptococci bacteria that belong to a group known as GAS (Group A Streptococci). S. pyogenes is known for its infectious properties and can cause a huge variety of diseases ranging from minor skin infections to sepsis to toxic shock syndrome. There are an estimated over 700 million cases per year worldwide of severe S. pyogenes infections. There is typically a 25% mortality associated with severe infections, which is largely due to failure to properly diagnose the infection in a timely manner. About 5-15% of healthy people harbor the bacterium in their respiratory tract but remain unaffected by it until they are immonucompromised.Clinically, differentiating among the groups of Steptococci is enormously important due to the fact that they can each cause different diseases and require different antibiotics. Group A strep are defined by the presence of antigen A on their cell wall, which can be detected by different serological tests. S. pyogenes not only displays the antigen A, but also something called the M protein that can be used to further classify sub groups of S. pyogenes. It should be no surprise that both antigen A and the M protein, along with an array of other surface antigens and exotoxins, are the reasons that the bacterium has enormous potential to cause human disease.

Cell Structure

Streptococcus pyogenes is a spherical, Gram positive bacterium. It is non-motile and non-spore forming. S. pyogenes can be differentiated from other group A strep by the presence of M factor on its cell well. Cells divide on a plane and exist in pairs or in chains.

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Methods of identification

There are many methods to rapidly and reliably indentify Streptococcus species and differentiate among the subgroups in a species. One of the broad identifiers is looking at the hemolytic properties. Streptococcus pyogenes is what is known as beta-hemolytic, meaning that it can lyse red blood cells. Due to this attribute, if you plate it on blood agar, the colonies appear to have clear “halos” surrounding them (see image below). This is due to a chemical called hyaluronic acid that is present in a capsule around the cells.
To get into differentiating among smaller subgroups: There are several different very closely relatedStreptococcus groups, and they can typically be differentiated by testing which polysaccharides and other antigens are displayed on their cell surface. One such test is the Lancefield antigen test, which is typically applied to categorize the Streptococcus into one of many different subgroups by assessing which antigens are displayed on the cell surface. Strep colonies are smeared onto a small card, and a colored reagent with antigen specific antibodies is poured over the smear. If the antibodies bind—or agglutinate, forming clumps—with the antigens in the strep smear, this means that the antigen in question is present (see lower image).
Getting into even greater specifics, Streptococcus pyogenes can be divided further still into subgroups. There is a lot of variation in the sequence of the emm gene, the gene that produces the M protein. Sequencing this gene to identify polymorphisms is now commonly used to group S. pyogenes into subgroups, and this test has largely replaced older biochemical tests. There have been over 140 emm types identified so far.

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Metabolism

S. pyogenes is a facultative anaerobe that needs enriched, blood-containing medium to grow. It is designated as "catalase negative" which means that it does not produce the enzyme catalase, an enzyme that catalyzes the reaction of hydrogen peroxide to water and oxygen. This is clinically significant, as a test for this enzyme is a common clinical diagnostic tool.

Infectious Diseases

The genome of S. pyogenes has been sequenced and was found to have more than 40 putative virulence genes. This is possibly why this bacterium is responsible for what might be the most diverse array of disease than known to be caused by any other bacterium. Most infections can betreated with an oral or intramuscular regimen of most beta-lactams such as penicillin or ampicillin,or other broad spectrum antibiotics such as vancomycin or clindamycin (though resistance to clindamycin is on the rise). Diseases it can cause include:

· Impetigo-- a superficial infection of the skin. Can be treated with antibiotics.
· Cellulitis-- an deep tissue infection
· Strep throat--an infection of the throat. Can be treated with antibiotics. However, if left untreated it can lead to Rheumatic fever and even endocarditis.
· Toxic shock syndrome (TSS)-- a couple species of bacteria can cause this. Symptoms include fever, dizziness, confusion, and mucous membrame hyperemia. It can result in organ failure. Typically, S. pyogenescaused TSS is a result of a skin infection. If properly diagnosed, it can be treated with antibiotics. If untreated or treated to late, can result in organ failure and death.
· Necrotizing fasciitis-- A disease that starts off as a superficial wound, but if that wound happens to have S. pyogenes with certain virulence genes, it can release exotoxins that destroy the host tissue. This is commonly known as "flesh eating bacteria", which a is a misnomer, because nothing is actually eating the tissue but rendering it necrotic with the release of exotoxins. Several other organisms can be responsible for this disease as well.Because of the swiftness and seriousness of this infection, amputation of infected parts isoften treatment.Symptoms include pain/discoloration that is disproportionate to the severity of a superficial wound, and sometimes even fever. Unfortunately, there is no "magic bullet" indicator of necrotizing fasciitis, but a number of factors that if present at certain levels in combination with the proper symptoms, indicate that infection is likely. If a medical professional suspects necrotizing fasciitis, he or she will look at six serological measurements: C reactive protein, white blood cell count, hemoglobin, sodium, creatnine, and glucose. These factors are scored, and a score of 6 or greater result in a diagnosis of the disease. The table below details the criteria:
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As mentioned, strep throat is one of the more common and usually minor forms of strep infection. The following video is a a creative and informative dramatization of a strep throat infection, from patient symptoms to diagnosis, to treatment- all acted out by Barbies.

Watch Video

Watch VideoStreptococcus pyogenes Infection [Barbie Version]
Duration: (7:49)
User: angle3

Streptococcus pyogenes and the mammalian immune system
One of the reasons S. pyogenes is so virulent is due in its ability to evade or interact with the mammalian immune system. Ways it can evade/interact with the immune system include:
· M protein allows it to evade phagocytosis by immune cells
· Hyaluronic acid capsule allows it to not only evade phagocytosis, but also may help it adhere to epithelial cells. Having this capsule can aid in obscuring the cell’s surface antigens, preventing immune cell recognition and subsequent response.
· Fibronectin binding protein and lipoteichoic acid help to adhere to mammalian cells

· Pyrogenic toxin is an exotoxin produced can cause the rash associated with scarlet fever and can also contribute to toxic shock syndrome.

Streptococcus pyogenes and super antigens

Super antigens are antigens produced by S. pyogenes that trigger the immune system. Lots of pathogens release antigens as a normal part of infection, and the immune system relies on a very specific "lock and key" fit for the presence of a foreign antigen to trigger an immune response. The "lock and key" fit ensure that only the right cells (cells that have a specific fit for the antigen you want to target) are stimulated. A super antigen will hyper-stimulate any and all immune cells, regardless for how well they will target an antigen.An analogy for this would be: the normal immune response is like a very good team of special forces that can adeptly target and attack invaders. The super antigen immune response is like a large but poorly trained army that attack with all their ammunition at once. This all out immune system "attack" can result in symptoms like severe fever and chills. See diagram below for a depiction of how superantigens work.

Full-size image (95 K)

Antibiotic resistance

Recently, there has been a rise in S. pyogenes that are resistant to broad spectrum antibiotics such as macrolide and clindomycin. Interestingly, S. pyogenes is one of the few species of pathogenic bacteria that have yet to develop resistance to beta-lactams. Bacitracin is one of the antibiotics that S. pyogenes is sensitive to, while many other species of strep are resistant to it. Thus, sensitivity to Bacitracin can be a good diagnostic to difeerentiate S. pyogenes from other species of strep. Below is a video demonstrating how one might do such a test.